title: Oxidized fatty acids: A potential pathogenic link between fatty liver and type 2 diabetes in obese adolescents?
abstract: In this study, we sought to investigate the putative association of the oxidized metabolites derived from linoleic acid (OXFAs) with pediatric nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D). We studied 80 obese adolescents (age 13.3 ± 3.31 years; body mass index 33.0 ± 6.79 kg/m(2)), who underwent an oral glucose tolerance test, a magnetic resonance imaging (MRI) to measure the hepatic fat content, and the measurement of OXFAs and caspase-cleaved Citokeratin18 fragment (CK-18), a robust biomarker of liver injury. In this study, we show that only in subjects with hepatic steatosis, the OXFAs are associated with the CK-18 and that this association is modulated by the PNPLA3 rs738409 variant. We also show that most of the OXFAs are associated with a lower insulin secretion and that adolescents with T2D have higher levels of OXFAs than subjects with impaired or normal glucose tolerance. These observations lead to the hypothesis that the OXFAs may be the pathogenic link between liver injury and T2D and that the novel therapeutic opportunities targeting the OXFAs are possible in adolescents with early-onset NAFLD and T2D.
authors.affiliation: 1 Department of Pediatrics, Yale University School of Medicine , New Haven, Connecticut.
authors.forename: Nicola
authors.initials: N
authors.lastname: Santoro
authors.forename: Sonia
authors.initials: S
authors.lastname: Caprio
authors.forename: Cosimo
authors.initials: C
authors.lastname: Giannini
authors.forename: Grace
authors.initials: G
authors.lastname: Kim
authors.forename: Romy
authors.initials: R
authors.lastname: Kursawe
authors.forename: Bridget
authors.initials: B
authors.lastname: Pierpont
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Shaw
authors.forename: Ariel E
authors.initials: AE
authors.lastname: Feldstein
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D005234:Fatty Liver / Q000150:complications / Q000235:genetics / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008049:Lipase / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000150:complications / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D020641:Polymorphism, Single Nucleotide; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D015415:Biomarkers; D005227:Fatty Acids; D005947:Glucose; D007328:Insulin; D008049:Lipase; D008565:Membrane Proteins; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent